The inhibitory effect of hydroalcoholic extract of black punica granatum pericarp on melanoma tumor angiogenesis through PPARα and PPARγ pathways in C57BL6 mice

Abstract

Background: Angiogenesis is the process of formation of new capillaries from the preexisting vessels and plays an important role in the growth and metastasis of tumor. In this study, we aimed to investigate the antiangiogenic effect of hydroalcoholic extract of black pomegranate pericarp extract (PPE) in the animal model of melanoma. Methods: The hydroalcoholic extract of black pomegranate pericarp was prepared using 70 ethanol containing 1 acetic acid. 1 × 106 B16F10 melanoma cells were injected to all mice on the day 0, subcutaneously (s.c). On 7th day, mice were divided into 9 groups of 8 animals. The first group received distilled water. Groups second to fifth received 50, 100, 200 and 400 mg/kg of black pomegranate pericarp extract. The sixth group received the extract and peroxisome proliferatoractivated receptor gamma (PPAR-γ) antagonist (5 mg/kg/day). The seventh group received the extract and PPAR-α antagonist (10 mg/kg/day). Eighth and ninth groups received fenofibrate (100 mg/kg) and rosiglitazone (100 mg/kg) as agonists of PPAR-α and PPAR-γ, respectively. On 16th day, mice were euthanized and their tumor samples were weighed and then analyzed via immunohistochemistry staining for CD31. Findings: The black pomegranate pericarp extract dose dependently decreased tumor weight and angiogenic marker (P < 0.05). Moreover, tumor weight and angiogenic marker in the groups which received both peroxisome prolIferator-activated receptor antagonists and black pomegranate pericarp extract, was more than the group which received the extract (P < 0.001). Level of angiogenesis and tumor weight in the groups which received fenofibrate and rosiglitazone was less than the group that received the highest dose of pomegranate pericarp extract (P < 0.05). Conclusion: Taken together, our observations suggest that black pomegranate pericarp extract may have potential implication in melanoma cancer treatment, and show that antiangiogenic effect of this extract may be mediated through modulation of peroxisome proliferator-activated receptor activation pathways. © 2015, Isfahan University of Medical Sciences(IUMS). All rights reserved.